Jaktinib Hydrochloride Tablets in Intermediate-risk and High-risk Myelofibrosis.
- Registration Number
- NCT03886415
- Lead Sponsor
- Suzhou Zelgen Biopharmaceuticals Co.,Ltd
- Brief Summary
This was an open-label, multi-center, randomized phase 2 study. This is a two-stage design.In the first stage, two dose groups were set up, the 100 mg bid dose group and the 200 mg qd dose group, which were randomized at 1:1, with 50 subjects in each group, and a total of 100 cases in the two groups. In the second stage, approximately 36 subjects were added to the randomized group.
- Detailed Description
According to the results of the interim analysis of the ZGJAK002 of Jaktinib, a comprehensive evaluation of the benefits and risks of subjects in the 100mg bid and 200mg qd groups, the investigator and the sponsor decided to expand the enrollment of approximately 36 subjects taking 100mg bid.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 118
Not provided
- Any significant clinical or laboratory abnormalities that the investigator considers to affect safety assessment, such as: a. uncontrolled diabetes (> 250 mg/dL, or 13.9 mmol > / L), b. had high blood pressure and antihypertensive drug treatment under two or unable to descend to the ranges (systolic blood pressure < 160 mmHg, diastolic pressure < 100 mmHg), c. peripheral neuropathy (NCI - CTC AE v4.03 standard grade 2 or above), d. thyroid dysfunction (> NCI - CTC AE v4.03 standard grade 2 or above);
- The patients had a history of congestive heart failure, uncontrollable or unstable angina or myocardial infarction, cerebrovascular accident or pulmonary embolism in the first 6 months;
- Screening of patients who have not fully recovered from surgery within the first 4 weeks;
- Screening for patients with arrhythmia requiring treatment or QTc interval (QTcB) >480ms;
- Screening for bacterial, viral, parasitic or fungal infections with any clinical symptoms that require treatment;
- Patients with a history of congenital or acquired hemorrhagic diseases;
- Patients who had previously undergone splenectomy or who had received radiotherapy of the splenic region within the first 12 months of screening;
- Screening for HIV positive, active hepatitis b virus positive (HBsAg positive, hbv- dna positive or greater than 1000 copies /ml), anti-hcv antibody or hcv-rna positive;
- Patients suffering from epilepsy or using psychotropic or sedative drugs at the time of screening;
- Women who are planning to become pregnant or who are pregnant or breast- feeding, as well as those who were unable to use effective contraceptives throughout the trial;Male patients who do not use condoms during the administration and within 2 days (approximately 5 half-lives) after the last administration;
- Patients who have suffered from malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years;
- Combined with other serious diseases, the researchers believe that patients' safety or compliance may be affected;
- Suspected allergic to Jakatinib hydrochloride or similar drugs;
- Patients who have participated in the clinical trials of other new drugs or medical devices within the first 3 months;
- Patients who were treated with any MF drug (e.g., hydroxyl urea), any immunomulator (e.g., thalidomide), any immunosuppressant, prednisone at or above 10mg/ day or equivalent bioactive level of glucocorticoid, growth factor (e.g.,erythropoietin ), or who were within 6 half-lives of the drug within 2 weeks prior to randomization;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Jaktinib hydrochloride tablets 1 Jaktinib hydrochloride tablets This is the dose group was given once a day. Jaktinib hydrochloride tablets 1 200mg qd dose group Jaktinib hydrochloride tablets 2 Jaktinib hydrochloride tablets This is the dose group was given twice a day. Jaktinib hydrochloride tablets 2 100mg bid dose group
- Primary Outcome Measures
Name Time Method effective rate 24 weeks The proportion of all subjects whose spleen volume decreased by 35% or more at 24 weeks
- Secondary Outcome Measures
Name Time Method Overall response rate （CR+PR） 24 weeks IWG-MRT efficacy criteria
MF related symptom response rate 24 weeks MPN-SAF TSS the proportion of patients whose total symptom score of the scale decreased by more than 50%;MPN-SAF TSS the total scale symptom score was lower than baseline
Progression-free survival (PFS) 24 weeks PFS was defined as the time from date of randomization to disease progression radiological or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of disease evaluation.
Overall survival (OS) 2 years OS is defined as the time from date of randomization to death due to any cause. Subjects without death at the time of analysis were censored at their last date of follow-up.
The spleen response 24 weeks The time from baseline to the first splenic volume reduction was greater than or equal to 35%；Optimal response: the proportion of patients whose spleen volume decreased by more than 35% compared with the baseline at least once;Effective time: the time from the randomization date to the first time the spleen volume decreased by more than 35% from the baseline；DoMSR: the time between the first occurrence of spleen volume reduction of more than 35% from the baseline to the increase of spleen volume less than 35% from the baseline;
Anemia response 24 weeks Baseline proportion of patients with blood transfusion dependence converted to patients without blood transfusion dependence（Patients without blood transfusion dependence: patients without red blood cell transfusion for more than 12 weeks during the treatment period and with HGB ≥85g/L）;The proportion of patients with baseline non-transfusion dependence (HGB ≤100g/L) whose HGB increased by 20g/L;RBC Infusion dependence decreased: RBC infusion frequency decreased by 50%;
Leukemia-free survival（LFS） 24 weeks The time elapsed between the dates of any of the following events from a randomized solstice；The first bone marrow smear showed that the original cells were more than 20% of the date；The initial peripheral blood smear showed that the original cells were more than 20% and A peripheral blood blast content of 20% associated with an absolute blast count of 1\*10(9)/L that lasts for at least 2 weeks；Death from any cause. Subjects without anyone of events at the time of analysis were censored at their last date of disease evaluation.
Trial Locations
- Locations (1)
The First Affiliated Hospital of Medical School of Zhejiang University
🇨🇳Hangzhou, Zhejiang, China